Dr. Rubel and Dr. Wang are currently investigating the important involvement of a calcium regulation protein, PMCA2, in the dendritic retraction of NL neurons. PMCA2 has an essential role in regulating intracellular calcium in the central nerve system and is densely expressed within NL dendritic branches. Preceding the deprivation-induced dendritic retraction, immunoreactivity of PMCA2 is significantly down-regulated in NL dendritic branches. More importantly, this down-regulation of PMCA2 is strongly associated with the dynamics of the proteins that are critical to the stabilization of dendritic cytoskeletons. The future work of Dr. Wang will focus on direct effects of PMCA2 on dendritic structure by manipulating the expression and function of PMCA2 using genetic and pharmacologic techniques. In addition, molecules and pathways that could influence the effect of PMCA2 on dendritic structure will also be investigated.

Genetic and behavior studies of Dr. Tempel further revealed that mutations in the PMCA2 gene lead to hearing loss and vestibulomotor deficits in mice. Over-expression of PMCA has been shown to protect cells from calcium-mediated apoptosis, another type of neuronal degeneration. Involvement of PMCA in dendritic reorganization could provide potential ways to pharmacologically prevent or treat dendritic degeneration and abnormalities, which may facilitate brain recovery from damages.

Research interests

Neuronal morphology is critical for normal brain function, including auditory information processing, and is subject to changes in neuronal activity caused by hearing loss, brain injury and diseases. Dendritic atrophy and abnormalities are major types of neuronal degeneration and contribute to a number of brain disorders. Prevention and treatments of dendritic degeneration require an understanding of the molecular substrates underlying the activity-dependent dendritic reorganization.

Dr. Edwin W Rubel, Dr. Bruce L Tempel, and Dr. Yuan Wang have been exploring the molecules and pathways involved in this dendritic reorganization in the auditory brainstem. Neurons in the nucleus laminaris (NL) are sensitive to interaural time differences (ITDs), the differences in the time of arrival of sound to the two ears. ITD is a critical cue for binaural processing, such as the localization of sound sources. Individual NL neurons have two separate sets of dendrites that receive acoustic inputs from the ipsilateral and contralateral ear, respectively. Stabilization of NL dendritic branches is one of the key requirements for maintaining balanced inputs between the two sets of dendrites, which in turn provides a foundation for accurate binaural processing. Dr. Rubel’s previous work found that removal of the inputs to one set of NL dendrites causes rapid and dramatic retraction of their branches within a couple of hours.

Figure: Left, Rapid and significant down-regulation of PMCA2 immunoreactivity in the NL dendritic domain whose inputs has been diminished, compared to the intact domain of the same neurons which receives normal inputs. Middle, Accompanying decrease of the immunoreactivity for the microtubule-associated protein 2, which is critical for the stabilization of dendritic cytoskeleton, in activity deprived dendritic branches. Right, the spectrum resulting from the middle panel showing more clearly the difference in the staining density between the two domains. White and red are for high density while green and blue for low density.

Publications:

1.         Wang Y, Karten HJ (2009). Three subdivisions of the auditory midbrain in chicks (Gallus gallus) identified by their afferent and commissural projections. J Comp Neurol. Accepted.

2.         Wang Y, Cunningham DE, Tempel BL, Rubel EW (2009) Compartment-specific regulation of plasma membrane calcium ATPase type 2 in the chick auditory brainstem. J Comp Neurol 514:624-640 pdf

3.         Wang Y, Rubel EW (2008). Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity. Neuroscience 154:381-389 pdf

4.         Gruberg E, Dudkin E, Wang Y, Marín G, Salas C, Sentis E, Letelier J, Mpodozis J, Malpeli J, Cui H, Ma R, Northmore D, Udin S (2006). Influencing and interpreting visual input: the role of a visual feedback system. J Neurosci 26:10368-10371 pdf

5.         Wang Y, Luksch H, Brecha NC, Karten HJ (2006). Columnar projections from the cholinergic nucleus isthmi to the optic tectum in chicks (Gallus gallus): a possible substrate for synchronizing tectal channels. J Comp Neurol 494: 7-35 pdf

6.         Wang Y, Major DE, Karten HJ (2004). Morphology and connections of nucleus isthmi pars magnocellularis in chicks (Gallu gallu). Journal of Comparative Neurology 469: 275-297 pdf

7.         Gu Y, Wang Y, Zhang T, Wang SR (2002). Stimulus size selectivity and receptive field organization of ectostriatal neurons in the pigeon. Journal of Comparative Physiology A 188: 173-178 pdf

8.         Gu Y, Wang Y, Wang SR (2002). Visual responses of neurons in the nucleus of the basal optic root to stationary stimuli in pigeons. Journal of Neuroscience Research 67: 698-704 pdf

9.         Wang Y, Gu Y, Wang SR (2001). Directional responses of basal optic neurons are modulated by the nucleus lentiformis mesencephali in pigeons. Neuroscience Letters 311: 33-36 pdf

10.      Gu Y, Wang Y, Wang SR (2001). Directional modulation of visual responses of pretectal neurons by accessory optic neurons in pigeons. Neuroscience 104: 153-159 pdf

11.      Wang Y, Xiao J, Wang SR (2000). Excitatory and inhibitory receptive fields of tectal cells are differentially modified by magnocellular and parvocellular divisions of the pigeon nucleus isthmi. Journal of Comparative Physiology A 186: 505-511 pdf

12.      Wang Y, Gu Y, Wang SR (2000). Modulatory effects of the nucleus of the basal optic root on rotundal neurons in pigeons. Brain, Behavior and Evolution 56: 287-292 pdf

13.      Wang Y, Gu Y, Wang SR (2000). Feature detection of visual neurons in the nucleus of the basal optic root in pigeons. Brain Research Bulletin 51: 165-169 pdf

14.      Gu Y, Wang Y, Wang SR (2000). Regional variation in receptive field properties of tectal neurons in pigeons. Brain, Behavior and Evolution 55: 221-228 pdf

15.      Xiao J, Wang Y, Wang SR (1999). Effects of glutamatergic, cholinergic and GABAergic antagonists on tectal cells in toads. Neuroscience 90: 1061-1067 pdf